2hqu
Human dUTPase in complex with alpha,beta-iminodUTP and magnesium ion
Structural highlights
FunctionDUT_HUMAN This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman dUTPase, essential for DNA integrity, is an important survival factor for cancer cells. We determined the crystal structure of the enzyme:alpha,beta-imino-dUTP:Mg complex and performed equilibrium binding experiments in solution. Ordering of the C-terminus upon the active site induces close juxtaposition of the incoming nucleophile attacker water oxygen and the alpha-phosphorus of the substrate, decreasing their distance below the van der Waals limit. Complex interactions of the C-terminus with both substrate and product were observed via a specifically designed tryptophan sensor, suitable for further detailed kinetic and ligand binding studies. Results explain the key functional role of the C-terminus. Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase.,Varga B, Barabas O, Kovari J, Toth J, Hunyadi-Gulyas E, Klement E, Medzihradszky KF, Tolgyesi F, Fidy J, Vertessy BG FEBS Lett. 2007 Oct 2;581(24):4783-8. Epub 2007 Sep 12. PMID:17880943[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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